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Updated: May 23, 2026
07:54
Cholesterol Efflux Assay
Published on: March 6, 2012
Rationale for cholesteryl ester transfer protein inhibition
Bernd Hewing1, Edward A Fisher
1Division of Cardiology (Preventive Cardiology), Department of Medicine, New York University School of Medicine, New York, New York 10016, USA.
Current Opinion in Lipidology
|April 21, 2012
Summary
Cholesteryl ester transfer protein (CETP) inhibitors raise HDL cholesterol to reduce cardiovascular risk. While early inhibitors like torcetrapib failed, newer agents like anacetrapib and dalcetrapib show promise, with ongoing trials to confirm cardiovascular benefits.
Area of Science:
- Cardiovascular medicine
- Pharmacology
- Lipid metabolism
Background:
- Raising high-density lipoprotein cholesterol (HDL-C) is a therapeutic goal for cardiovascular risk reduction.
- Cholesteryl ester transfer protein (CETP) inhibition significantly increases HDL-C levels.
- The cardiovascular outcome benefits of CETP inhibition require further establishment.
Purpose of the Study:
- To review the current status of cholesteryl ester transfer protein (CETP) inhibitors as a therapeutic strategy for lowering cardiovascular risk.
- To evaluate the efficacy and safety of various CETP inhibitors in clinical trials.
- To discuss the ongoing outcome trials investigating the role of CETP inhibition in cardiovascular disease.
Main Methods:
- Review of clinical trial data for CETP inhibitors, including phase II and phase III studies.
- Analysis of lipid profile changes and adverse events associated with different CETP inhibitors.
- Focus on outcome trials such as ILLUMINATE, DEFINE, dal-VESSEL, dal-PLAQUE, dal-OUTCOMES, and REVEAL.
Main Results:
- Torcetrapib (first-in-class CETP inhibitor) failed due to increased mortality and cardiovascular events, linked to off-target effects.
- Anacetrapib demonstrated significant HDL-C increase (~138%) and LDL-C decrease (~40%) without adverse effects.
- Dalcetrapib showed a moderate HDL-C increase (~30%) with proven safety, while evacetrapib exhibited favorable lipid changes in phase II.
Conclusions:
- Ongoing outcome trials (dal-OUTCOMES and REVEAL) are crucial for determining the effectiveness of CETP inhibition in reducing cardiovascular risk.
- The success of anacetrapib and dalcetrapib warrants further investigation into their role in cardiovascular disease prevention.
- CETP inhibition remains a promising, yet not fully validated, strategy for managing cardiovascular risk through HDL-C elevation.
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